The present invention relates to a nuclear magnetic resonance apparatus probe and a nuclear magnetic resonance apparatus using the same.
Analysis methods for organic substances employing nuclear magnetic resonance have been making a rapid progress these days. In particular, when the methods are combined with a powerful superconducting magnet technology, it has become possible to make an efficient structural analysis on an atomic level of organic compounds, such as protein having a complicated molecular structure. The present invention is concerned with a nuclear magnetic resonance apparatus used for analyzing the structure and interaction on an atomic level of protein molecules in an aqueous solution, in which a trace amount of protein is dissolved. Namely, the invention is concerned with an energy spectrometer, of which a more outstanding performance is required than medical MRI computerized tomography scanners that are intended for computerized tomography scanning of human bodies and that must therefor offer image resolution on the order of millimeters. More specifically, the performance required includes an order of magnitude greater in terms of magnetic field strength, four orders of magnitude greater in terms of magnetic field homogeneity, and three orders of magnitude greater in terms of stability. More particularly, it is concerned with a probe coil used therein.
The nuclear magnetic resonance apparatus may be generally classified into a CW type, in which a sample is irradiated with electromagnetic waves of a constant frequency and a pulse Fourier type, in which the sample is irradiated with pulsating electromagnetic waves. Lately, however, the nuclear magnetic resonance apparatus refers in many cases to the pulse Fourier type and, in the present invention, too, the pulse Fourier type nuclear magnetic resonance apparatus is simply referred to as the nuclear magnetic resonance apparatus unless otherwise specified.
Basic configurations of the nuclear magnetic resonance apparatus are described in the book entitled “On NMR” (authored by Yoji Arata and published by Maruzen in 2000). According to the book, a nuclear magnetic resonance apparatus may be composed of a superconducting magnet that produces a static magnetic field, a probe that is capable of exposing the sample to an RF pulse magnetic field so as to produce a precession movement in a magnetization vector of an atomic nucleus and of receiving a free induction decay signal (FID signal) emitted from the sample, an RF power source that supplies the probe with an RF current, an amplifier that amplifies the FID signal, a detector that detects a signal, an analyzer that analyzes the signal detected by the detector, and the like. The probe is generally provided with a probe coil that is generally provided with functions of exposing the sample to the RP pulse magnetic field and receiving the FID signal emitted by the sample.
There are known, as recent inventions relating to typical configurations of the nuclear magnetic resonance apparatus as it is used for the analysis of protein, Japanese Patent Laid-open No. 2000-147082 and the like that disclose a typical configuration employing a multilayer air-core solenoid coil as an invention relating to the superconducting magnet, U.S. Pat. No. 6,121,776 that discloses a bird-cage type probe coil as an invention relating to signal detection technology, and Japanese Patent Laid-open No. 2000-266830, Japanese Patent Laid-open No. Hei 6-237912, and the like that disclose signal detection technology by means of a conventional saddle type probe coil or a bird-cage type probe coil. According to these inventions, there are provided in all of these conventional, high-sensitivity nuclear magnetic resonance apparatuses for use in protein analysis a superconducting magnet apparatus that produces a magnetic field in a perpendicular direction and a saddle type or bird-cage type probe coil that is capable of exposing the sample to an RP pulse magnetic field and receiving an FID signal emitted from the sample. In addition, as exemplified in U.S. Pat. No. 6,121,776, there is known a case, in which a probe coil that is cooled down to low temperatures so as to reduce thermal noise during signal reception is employed to improve the signal-to-noise ratio, or S/N ratio. As regards effects of improved sensitivity produced by the probe coil shape, it has conventionally been known that the use of a solenoid coil as the probe coil is more advantageous in many respects than using the saddle type or bird-cage type, as described in the book entitled “On NMR”. The use of the solenoid coil is advantageous in terms, for example, of ease of impedance control, filling factor, and efficiency in the RF magnetic field. Since it is necessary, with the superconducting magnet that produces the magnetic field in the perpendicular direction, to irradiate the sample with the RF pulse magnetic field in the horizontal direction, however, it is impracticable to wind the solenoid coil around a sample tube in the perpendicular direction containing therein an aqueous solution of protein, and thus it is not commonly used. Particularly exceptionally, however, there has been known a case, in which the solenoid coil is used only for measurement with a good sensitivity using a trace amount of sample solution and there has been known a measurement method that takes measurement using a specially designed micro-sample tube and a special probe. Nonetheless, it is generally required that the static magnetic field be horizontal in order to employ a solenoid coil as the nuclear magnetic resonance apparatus probe for major use in protein analysis.
In order to employ a solenoid coil as the probe coil, there is a problem that it is difficult to install a plurality of coils to permit simultaneous measurement of different nuclides, or what is called multiple resonance. This will be elaborated upon in the following.
The probe coil is designed to resonate at a frequency of an RF pulse magnetic field. Assuming that the probe coil has a circuit configuration, in which a resistance component (resistor R), an electromagnetic induction component (inductance L), and an electrostatic capacity component (capacitance C) are connected in series with each other, a resonance frequency fo is given by equation 1.
                              f          0                =                  1                      2            ⁢                                                  ⁢            π            ⁢                          LC                                                          Equation        ⁢                                  ⁢        1            
A Q-value Q that is a factor representing intensity of resonance is given by equation 2.
                    Q        =                                            L              C                        ⁢                          1              R                                                          Equation        ⁢                                  ⁢        2            
As is known from equation 1 and equation 2, it is possible to define the resonance frequency fo and the Q-value by the combination of inductance L and capacitance L; however, a different nuclide results in a different resonating frequency and it is difficult to implement multiple resonance using a simple circuit. Commonly employed methods include one in which the Q-value is kept low and a circuit is organized to respond to a plurality of resonance frequencies, one in which only one coil is installed, but the resonance frequency is switched by changing the capacitance C, and one in which a plurality of independent circuits are provided, each providing a specific required resonance frequency. According to the first method, the low Q-value results in a radiation loss of the RF pulse and, in addition, the FID signal is small, which makes it difficult to improve the S/N ratio. In the second method, it is difficult to implement quick switching. In the third method, interference caused by electromagnetic induction among different coils presents a problem. According to the conventional nuclear magnetic resonance apparatuses, therefore, the saddle type coil is disposed so that the RF pulse magnetic fields produced are orthogonal to each other. FIG. 1 is a view showing a layout of saddle type coils in a conventional nuclear magnetic resonance apparatus. FIG. 2 is a view showing a layout the saddle type coils shown in FIG. 1 seen from the above. A saddle type coil 110a and a saddle type coil 101b are disposed so as to be opposed to each other in a manner to surround a sample tube 100 and connected in series with each other electrically. A saddle type coil 102a and a saddle type coil 102b are also disposed so as to be opposed to each other and connected in series with each other electrically. A pair of saddle type coils 101, 102 are disposed so as to be orthogonal to each other. A static magnetic field direction 1 runs parallel with an axial direction of the sample tube 100. A capacitor is connected to a position near each of the saddle type coils and adjusted so as to deliver a desired resonance frequency. In the conventional nuclear magnetic resonance apparatus, in which the static magnetic field runs in the perpendicular direction, two pairs of saddle type coils are disposed so as to be orthogonal to each other, thereby making interference caused by electromagnetic induction between coils small, thus realizing multiple resonance.
In a nuclear magnetic resonance apparatus having a static magnetic field in a horizontal direction and employing a solenoid coil as the probe coil, however, it is geometrically impossible to dispose a plurality of solenoid coils so as to be orthogonal to each other around the sample tube, thus being unable to realize multiple resonance.